title: Papillary squamous cell carcinoma of the head and neck: clinicopathologic and molecular features with special reference to human papillomavirus.
abstract: A relationship between human papillomavirus (HPV) infection and papillary squamous cell carcinoma (PSCC) has been suggested. However, to date, no studies have thoroughly and directly evaluated for transcriptional activity of the virus or the clinicopathologic significance of HPV-positive PSCC. Forty-eight cases of PSCC were retrieved from our surgical pathology database and were reviewed by 4 study pathologists, with tumors defined as SCC with a significant component of papillary growth in the tumor. Immunohistochemical analysis for p16 and p53 was performed. Overexpression of p16 was used as a surrogate marker of transcriptionally active HPV. Transcriptional activity was also directly evaluated using RNA in situ hybridization to detect high-risk HPV E6/E7 mRNA. Clinical follow-up data were obtained by chart review. Seven cases were located in the oral cavity, 19 in the oropharynx, and 22 in the larynx. Two morphologic types of PSCC were identified: keratinizing type, in which the epithelial cells showed a maturation trend with minimal surface parakeratin, and nonkeratinizing type, in which the papillae were completely covered by immature basaloid cells. Transcriptionally active HPV was present in 23 of 43 (53.4%) tumors. The majority of tumors harboring transcriptionally active HPV arose in the oropharynx, showed nonkeratinizing morphology, were p16 positive, and p53 negative. Transcriptionally active HPV was also present in many laryngeal and oral cavity PSCCs. Overall survival, disease-specific survival, and disease-free survival were favorable and did not significantly differ by anatomic subsite. However, HPV-related tumors showed a trend toward better survival.
authors.affiliation: Departments of *Pathology and Immunology †Department of Otolaryngology Head and Neck Surgery §Division of Biostatistics, Washington University School of Medicine, St Louis, MO ‡Advanced Cell Diagnostics Inc., Hayward, CA.
authors.forename: Mitra
authors.initials: M
authors.lastname: Mehrad
authors.forename: Danielle H
authors.initials: DH
authors.lastname: Carpenter
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Chernock
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ma
authors.forename: Yuling
authors.initials: Y
authors.lastname: Luo
authors.forename: Jingqin
authors.initials: J
authors.lastname: Luo
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Samir K
authors.initials: SK
authors.lastname: El-Mofty
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology / Q000821:virology*; D016009:Chi-Square Distribution; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000821:virology; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D012307:Risk Factors; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53